The present invention relates to 1H-phenalene-1-one derivatives, and the production and use thereof.
The active or passive penetration, adhesion and multiplication of pathogens in a host is called infection. Sources for infectious particles occur everywhere. Thus, for example, the human body is colonized by a large number of microorganisms which, as a rule, are kept under control by the normal metabolism and a sound immune system. However, for example if the immune system is weakened, a proliferation of the pathogens and, depending on the type of pathogenic agent, different symptoms can result. Doctors hold ready specific antagonists for many diseases caused by pathogenic agents, for example antibiotics to counter bacteria or antimycotics to counter fungi or virostatics to counter viruses. However, with the use of these antagonists, the occurrence of resistant pathogens, which sometimes have resistance to several antagonists at the same time, is increasingly to be observed. The treatment of infectious diseases has become increasingly difficult because of the occurrence of these resistant or multi-resistant pathogens. The clinical consequence of resistance is manifested by a failure of the treatment, above all in immunosuppressed patients.
New starting points for the fight against resistant or multi-resistant germs are therefore firstly the search for new antagonists, for example antibiotics or antimycotics, and secondly the search for alternative inactivation possibilities.
Photodynamic inactivation of microorganisms has proved its worth as an alternative method. Two different photo-oxidative processes play a decisive role in the photodynamic inactivation of microorganisms. On the one hand, the presence of a sufficient quantity of oxygen and, on the other hand, the localization of a so-called photosensitizer which is excited by light of a corresponding wavelength are prerequisites for the progress of a photo-oxidative inactivation. The excited photosensitizer can bring about the formation of reactive oxygen species (ROS), wherein on the one hand radicals, for example superoxide anions, hydrogen peroxide or hydroxyl radicals, and/or on the other hand excited molecular oxygen, for example singlet oxygen, can be formed.
In both reactions, the photo-oxidation of specific biomolecules which are located in direct proximity of the reactive oxygen species (ROS) is of primary importance. In particular an oxidation of lipids and proteins which occur for example as constituents of the cell membrane of microorganisms takes place. The destruction of the cell membrane in turn results in the inactivation of the microorganisms concerned. A similar elimination process is adopted for viruses and fungi.
For example, all molecules are attacked by singlet oxygen. However, unsaturated fatty acids in the membranes of bacteria are particularly susceptible to damage. Healthy cells belonging to the body have a cellular defense against attacks by free radicals, so-called catalases or superoxide dismutases. Healthy cells belonging to the body can therefore counteract damage by reactive oxygen species (ROS), for example radicals or singlet oxygen.
Numerous photosensitizers are known from the state of the art which originate for example from the group of porphyrins and derivatives thereof or phthalocyanines and derivatives thereof or fullerenes and derivatives thereof or derivatives with phenothiazinium structure, such as for example methylene blue or toluidine blue, or representatives of the phenoxazinium series, such as for example Nile blue. The photodynamics of methylene blue or toluidine blue against bacteria are already used for example in dentistry.
The photosensitizers known from the state of the art are usually substances with a relatively complex molecular structure and therefore expensive production methods.
It is known that 1H-phenalene-1-one and sulfonated 1H-phenalene-1-one have high yields of singlet oxygen, wherein however the affinity to microorganisms is low. It is furthermore known that singlet oxygen can diffuse only over a small distance before it reacts or is disintegrated. The inactivation of microorganisms by 1H-phenalene-1-one and sulfonated 1H-phenalene-1-one is therefore insufficient.
Hair-coloring compositions based on phenalenone derivatives are known from GB 2 337 530 A in which the ring carbon atoms can be directly substituted by an aminodialkyl group.
An object of the present invention is therefore to provide novel photosensitizers which inactivate microorganisms more efficiently.